Metabolism of aflatoxin B1 in the isolated nuclei of rat liver.
The nuclear biotransformation of aflatoxin B1 in vitro was observed with regard to inducer specificity, pH dependency, time course, kinetics, inhibitor sensitivity, and nuclear localization, and these data were compared with those from the microsomal transformation of aflatoxin B1. The nuclei and microsomes are capable of metabolizing aflatoxin B1 into aflatoxin M1, aflatoxin Q1, and two unidentified fluorescent compounds in the presence of fortified NADPH generating system. Pretreatments of rats by 3-methylcholanthrene or polychlorinated biphenyl enhanced both the nuclear and microsomal C-9 alpha-hydroxylation of aflatoxin B1 into aflatoxin M1 and phenobarbital or polychlorinated biphenyl induced aflatoxin Q1 production. The optimal pHs for aflatoxin M1 and Q1 were 8.3 and 7.4, respectively, both in the nuclei and microsomes. Kinetic analysis revealed the Km of aflatoxin M1 formation in methylcholanthrene-induced nuclei was 9.4 x 10(-5) M, and this value was very close to that obtained with the microsomes. Inhibitor experiments revealed a high sensitivity of aflatoxin M1 formation to 7,8-benzoflavone and a low sensitivity of aflatoxin Q1 to SKF 525A. These findings and data on the detergent treatment of nuclei suggest that the nuclear cytochrome P-448 system, induced by 3-methylcholanthrene and localized in the outer membrane, catalyzes the aflatoxin M1 formation, and the cytochrome P-450 system induced by phenobarbital biotransforms aflatoxin B1 into aflatoxin Q1. Pretreatment of rats by phenobarbital was found to induce microsomal degradation or detoxication of aflatoxin B1 into water-soluble metabolites, and no such an induction was observed in the nuclei.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002467:Cell Nucleus / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats
D000348:Aflatoxins; D011092:Polyethylene Glycols; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase